Biology subjects

Kanamarlapudi, V.

Publications and source records attributed to Kanamarlapudi, V..

2 recordsLinked to original sources

bioRxiv2022

EFA6R suppresses ovarian cancer cell migration and invasion

Exchange factor for ADP-ribosylation factor (Arf)6 (EFA6)R expression loss in ovarian cancer has shown to decrease patient survival. EFA6R contains the catalytic Sec7, pleckstrin homology (PH), and coiled-coil (CC) domains. To gain further insight into the role of EFA6R, this study further investigated EFA6R expression in OC and its putative role as a metastatic suppressor. EFA6R mRNA expression, assessed by RT-qPCR, was significantly downregulated in OC tissues and cell lines. OC tissue microarray staining with EFA6R antibody showed that loss of protein expression correlated with increased cancer grade. Furthermore, EFA6R protein levels, assessed by immunoblotting, were significantly reduced in OC tissues and cell lines. Treatment of SKOV-3 cells with 5-aza-2deoxycytidine, an epigenetic regulator, restored EFA6R expression and attenuated functional cell migration and invasion, which was reversed by siRNA-mediated knockdown of EFA6R expression. This study also revelated that exogenously expressed EFA6R localises to the plasma membrane, through its PH domain, and thereby inhibits cell migration and invasion in the CC domain-dependent and an Arf6-independent manner. EFA6R loss-of-function involves epigenetic mechanisms in which downregulation increases OC tumour cell migration and invasion. Summary statementEFA6R expression is epigenetically regulated in ovarian cancer cells and loss of expression correlates with increased tumour grade and enhanced tumour cell migration. EFA6R appears to mediate these effects independently of Arf6.

cell biology↗

bioRxiv2017

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

It is not clear why central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 positive carriers. We reasoned that this exclusion might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this hypothesis using laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 GEF EFA6. EFA6 exerts its effects from a previously unreported location within the axon initial segment (AIS). EFA6 does not localise here in DRG axons, and in these neurons, ARF activation is counteracted by an ARF-GAP which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whilst overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the axon initial segment, signalling and transport.\n\nSummary StatementWe identify a novel resident of the axon initial segment, EFA6. This functions to prevent growth-promoting molecules from entering mature CNS axons. Removing EFA6 elevates the axons regenerative potential.

cell biology↗